Identification of the tyrosine phosphatase PTP-MEG2 as an antagonist of hepatic insulin signaling

SummaryInsulin resistance is a primary defect in type 2 diabetes characterized by impaired peripheral glucose uptake and insufficient suppression of hepatic glucose output. Insulin signaling inhibits liver glucose production by inducing nuclear exclusion of the gluconeogenic transcription factor FOXO1 in an Akt-dependent manner. Through the concomitant application of genome-scale functional screening and quantitative image analysis, we have identified PTP-MEG2 as a modulator of insulin-dependent FOXO1 subcellular localization. Ectopic expression of PTP-MEG2 in cells inhibited insulin-induced phosphorylation of the insulin receptor, while RNAi-mediated reduction of PTP-MEG2 transcript levels enhanced insulin action. Additionally, adenoviral-mediated depletion of PTP-MEG2 in livers of diabetic (db/db) mice resulted in insulin sensitization and normalization of hyperglycemia. These data implicate PTP-MEG2 as a mediator of blood glucose homeostasis through antagonism of insulin signaling, and suggest that modulation of PTP-MEG2 activity may be an effective strategy in the treatment of type 2 diabetes

Use of Korean dramas to facilitate precision mental health understanding and discussion for Asian Americans

Precision mental health holds great potential for revolutionizing care and reducing the burden of mental illness. All races and ethnicities such as Asian Americans, the fastest growing racial group in the United States (U.S.), need to be engaged in precision mental health research. Owing to its global popularity, Korean drama ('K-drama') television shows may be an effective educational tool to increase precision mental health knowledge, attitudes and behaviors among Asian Americans. This qualitative study examined the participants' perspectives about and acceptance of using K-dramas to educate and engage Asian Americans about precision mental health. Twelve workshops were conducted in English, Vietnamese and Korean with a convenience sample in the San Francisco Bay Area in the U.S. (n = 122). Discussions were coded for themes. Findings revealed that all language groups reported positive reactions to using K-dramas to learn about precision health, genetics and mental health. Overall, participants shared that they learned about topics that are not generally talked about (e.g. precision health; genetic testing; mental health), from other people's perspectives, and the importance of mental health. Participants expressed how much they enjoyed the workshop, how they felt relieved due to the workshop, thought the workshop was interesting, and had an opportunity for self-reflection/healing. This pilot test demonstrated that K-dramas has promise to be used as a health educational tool in a workshop format focused on mental health among a diverse group of Asian Americans. Given the widespread access to K-dramas, they present a scalable opportunity for increasing awareness about specific health topics

Explaining Foreign Holdings of Asia's Debt Securities: The Feldstein-Horioka Paradox Revisited

In this paper, we find that home bias is still present in all economies and regions, especially in the case of short-term debt securities, but that there are substantial variations among economies and regions in the strength of home bias, with the Eurozone economies, the US, and developing Asia showing relatively weak home bias and advanced Asia, especially Japan, showing relatively strong home bias. We then examine trends over time in foreign holdings of debt securities and find that capital has been flowing from the US and the Eurozone economies to both advanced Asia (especially Japan) and developing Asia and that foreign holdings of debt securities have been increasing in advanced as well as developing Asia but for different reasons. The main reason in the case of advanced Asia (especially Japan) appears to be higher riskadjusted returns, whereas the main reason in the case of developing Asia appears to be the growth of debt securities markets combined with relatively weak home bias and (in the case of short-term securities) lower exchange rate volatility. Finally, we find that since the Global Financial Crisis, foreign holdings of debt securities have declined (i.e., that home bias has strengthened) in all economies and regions except developing Asia, where they have increased (except for a temporary decline in 2008) but where their share is still much lower than the optimal share warranted by the capital asset pricing market model

Therapeutic Drug Monitoring in Non-Tuberculosis Mycobacteria Infections

Nontuberculous mycobacteria can cause minimally symptomatic self-limiting infections to progressive and life-threatening disease of multiple organs. Several factors such as increased testing and prevalence have made this an emerging infectious disease. Multiple guidelines have been published to guide therapy, which remains difficult owing to the complexity of therapy, the potential for acquired resistance, the toxicity of treatment, and a high treatment failure rate. Given the long duration of therapy, complex multi-drug treatment regimens, and the risk of drug toxicity, therapeutic drug monitoring is an excellent method to optimize treatment. However, currently, there is little available guidance on therapeutic drug monitoring for this condition. The aim of this review is to provide information on the pharmacokinetic/pharmacodynamic targets for individual drugs used in the treatment of nontuberculous mycobacteria disease. Lacking data from randomized controlled trials, in vitro, in vivo, and clinical data were aggregated to facilitate recommendations for therapeutic drug monitoring to improve efficacy and reduce toxicity

The s ---> d gamma decay in and beyond the Standard Model

The New Physics sensitivity of the s ---> d gamma transition and its accessibility through hadronic processes are thoroughly investigated. Firstly, the Standard Model predictions for the direct CP-violating observables in radiative K decays are systematically improved. Besides, the magnetic contribution to epsilon prime is estimated and found subleading, even in the presence of New Physics, and a new strategy to resolve its electroweak versus QCD penguin fraction is identified. Secondly, the signatures of a series of New Physics scenarios, characterized as model-independently as possible in terms of their underlying dynamics, are investigated by combining the information from all the FCNC transitions in the s ---> d sector.Comment: 54 pages, 14 eps figure

Toward reconstructing the evolution of advanced moths and butterflies (Lepidoptera: Ditrysia): an initial molecular study

<p>Abstract</p> <p>Background</p> <p>In the mega-diverse insect order Lepidoptera (butterflies and moths; 165,000 described species), deeper relationships are little understood within the clade Ditrysia, to which 98% of the species belong. To begin addressing this problem, we tested the ability of five protein-coding nuclear genes (6.7 kb total), and character subsets therein, to resolve relationships among 123 species representing 27 (of 33) superfamilies and 55 (of 100) families of Ditrysia under maximum likelihood analysis.</p> <p>Results</p> <p>Our trees show broad concordance with previous morphological hypotheses of ditrysian phylogeny, although most relationships among superfamilies are weakly supported. There are also notable surprises, such as a consistently closer relationship of Pyraloidea than of butterflies to most Macrolepidoptera. Monophyly is significantly rejected by one or more character sets for the putative clades Macrolepidoptera as currently defined (<it>P </it>< 0.05) and Macrolepidoptera excluding Noctuoidea and Bombycoidea sensu lato (<it>P </it>≤ 0.005), and nearly so for the superfamily Drepanoidea as currently defined (<it>P </it>< 0.08). Superfamilies are typically recovered or nearly so, but usually without strong support. Relationships within superfamilies and families, however, are often robustly resolved. We provide some of the first strong molecular evidence on deeper splits within Pyraloidea, Tortricoidea, Geometroidea, Noctuoidea and others.</p> <p>Separate analyses of mostly synonymous versus non-synonymous character sets revealed notable differences (though not strong conflict), including a marked influence of compositional heterogeneity on apparent signal in the third codon position (nt3). As available model partitioning methods cannot correct for this variation, we assessed overall phylogeny resolution through separate examination of trees from each character set. Exploration of "tree space" with GARLI, using grid computing, showed that hundreds of searches are typically needed to find the best-feasible phylogeny estimate for these data.</p> <p>Conclusion</p> <p>Our results (a) corroborate the broad outlines of the current working phylogenetic hypothesis for Ditrysia, (b) demonstrate that some prominent features of that hypothesis, including the position of the butterflies, need revision, and (c) resolve the majority of family and subfamily relationships within superfamilies as thus far sampled. Much further gene and taxon sampling will be needed, however, to strongly resolve individual deeper nodes.</p

Study of Zγ events and limits on anomalous ZZγ and Zγγ couplings in pp̄ collisions at s=1.96TeV

We present a measurement of the Zγ production cross section and limits on anomalous ZZγ and Zγγ couplings for form-factor scales of Λ=750 and 1000 GeV. The measurement is based on 138 (152) candidates in the eeγ (μμγ) final state using 320(290)pb-1 of pp̄ collisions at s=1.96TeV. The 95% C.L. limits on real and imaginary parts of individual anomalous couplings are |h10,30Z|<0.23, |h20,40Z|<0.020, |h10,30γ|<0.23, and |h20,40γ|<0.019 for Λ=1000GeV. © 2005 The American Physical Society

Prevalence and factors associated with traditional herbal medicine use among patients on highly active antiretroviral therapy in Uganda

<p>Abstract</p> <p>Background</p> <p>In Africa, herbal medicines are often used as primary treatment for Human immunodeficiency virus (HIV) related problems. Concurrent use of traditional herbal medicines (THM) with antiretroviral drugs (ARVs) is widespread among HIV infected patients. However, the extent of THM use is not known in most settings in Sub-Saharan Africa. This study aimed at determining the prevalence and factors associated with THM use among HIV infected patients on highly active antiretroviral therapy (HAART) attending The AIDS Support Organization (TASO) in Uganda. TASO is a non-governmental organization devoted to offering HIV/AIDS care and treatment services in the population.</p> <p>Methods</p> <p>This was a cross-sectional study carried out in two TASO treatment centres in Uganda among 401 randomly selected eligible participants. We included participants who were 18 years and above, were enrolled on HAART, and consented to participate in the study. Data was collected using an interviewer-administered semi-structured questionnaire. THM use referred to someone who had ever used or was currently using herbal medicine while on highly active antiretroviral therapy (HAART) by the time of the study. Data was captured in Epi-data version 3.1 and exported to STATA version 9.0 for analysis.</p> <p>Results</p> <p>The prevalence of THM use was 33.7%. Patients on HAART for < 4 years were more likely to use THM (OR = 5.98, 95% CI 1.13 - 31.73) as well as those who experienced HAART side effects (OR = 3.66, 95% CI: 1.15 - 11.68). Older patients (≥39 years) were less likely to use THM (OR = 0.26 95% CI: 0.08 - 0.83). Participants with HAART adherence levels > 95% were less likely to use THM (OR = 0.09, 95% CI 0.01 - 0.65).</p> <p>Conclusion</p> <p>The prevalence of THM use among participants on HAART was high. This raises clinical and pharmacological concerns that need attention by the health care service providers.</p

Measurement of the B0_s semileptonic branching ratio to an orbitally excited D_s** state, Br(B0_s -> Ds1(2536) mu nu)

In a data sample of approximately 1.3 fb-1 collected with the D0 detector between 2002 and 2006, the orbitally excited charm state D_s1(2536) has been observed with a measured mass of 2535.7 +/- 0.6 (stat) +/- 0.5 (syst) MeV via the decay mode B0_s -> D_s1(2536) mu nu X. A first measurement is made of the branching ratio product Br(b(bar) -> D_s1(2536) mu nu X).Br(D_s1(2536)->D* K0_S). Assuming that D_s1(2536) production in semileptonic decay is entirely from B0_s, an extraction of the semileptonic branching ratio Br(B0_s -> D_s1(2536) mu nu X) is made.Comment: 7 pages, 2 figures, LaTeX, version with minor changes as accepted by Phys. Rev. Let